drugs may reduce cognitive decline

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Psychologist’s mother Daniela Grolli he was 62 when he started having episodes of forgetfulness. Remembering everyday tasks or family commitments became increasingly difficult, however, it was only a few years later, aged 67, that Jocelira Grolli was finally diagnosed with Alzheimer’s disease.

A few months later, in early 2022, she underwent additional tests and started receiving specific medications to treat her symptoms.

Although more than 55 million people around the world live with the disease, according to data from the World Health Organization (WHO), current medications, such as the ones Jocelira takes, do not act directly on the mechanisms that cause the disease. Currently, the drugs available in Brazil have the role of delaying the progression of symptoms.

However, this scenario may change in the coming years with the development of drugs that act against the accumulations of protein that form in the brain of Alzheimer’s patients.

Experimental drugs for treating Alzheimer’s

One of these drugs is lecanemabe, which had new results released in November last year. According to the manufacturers Eisai and Biogen, the drug is able to reduce cognitive deterioration by up to 27% in patients, compared to the group that received a placebo.

O lecanemabe was tested with 1,795 patients from 14 countries who had Alzheimer’s symptoms mild and accumulation of beta-amyloid proteins in the brain. In these tests, it was identified that in addition to reducing the deterioration caused by the disease, the drug caused 26% cognitive improvement and 36% improvement in functionality in 18 months of treatment.

Because of these results, the American drug regulatory agency, the Federal Drug Administration (FDA, its acronym in English), granted in January of this year an approval for an accelerated route for the drug, which should be sold in the country for US$ 26,000 per year, according to the manufacturer.

Another drug that works similarly, called aducanumab, was also approved for clinical use in the US, in a controversial and accelerated FDA review process. Given this scenario, the substance also significantly reduced the “clumps” of beta-amyloid proteins in the brain.

However, the clinical outcome of aducanumabthat is, the improvement observed in patients after this reduction in accumulated proteins, was considered less than expected.

The side effects of the drug were considered very serious. Another obstacle is that the commercial version of the drug, called Aduhelmcame to market at a high cost — around $56,000 per year per patient in the US.

Experts study other treatment possibilities

“Aducanumab proved to be effective in removing these plaques and proteins, but it was not effective in clinical studies, in the symptoms of patients. So there was a controversy, a doubt about the need to approve it so quickly. Nowadays, most doctors have already stopped using this drug. There was a great discussion in the scientific community”, says the neurologist Ivan Okamotomember of the Center for Excellence in Memory at Hospital Israelita Albert Einstein and coordinator of the Memory Institute at the Federal University of São Paulo (Unifesp).

To the Vice President of Brazilian Society of Geriatrics and Gerontology (SBGG), Marco Túlio Cintra, the development of these two alternatives represents hope because almost 20 years ago there were no new drugs against Alzheimer’s approved by the FDA.

Despite the positive numbers, doctors call for caution in the analysis since the two main drugs under study are indicated only for patients with mild Alzheimer’s.

“It is hope, no doubt, but perhaps it is hope for those at high risk of developing the disease, for those with a family history. If the person already has Alzheimer’s, even if it’s mild, it may be that, by the time the whole process is finished, they already have the moderate form, and then [ela] is not the target audience”, explains Cintrawho is also a professor at the Federal University of Minas Gerais (UFMG).

The drugs currently being used in patients with the disease seek to reduce the speed of the decline, and not to act on the mechanisms that cause the deterioration in the brain. The new generation — aducanumab and lecanemab — seeks to break with this logic. They focus on the ability to act against one of the main mechanisms of Alzheimer’s, which is the accumulation of beta-amyloid proteins in the brain.

While these drugs are effective at targeting protein plaques, it remains to be seen whether this “cleanup” is enough to reverse Alzheimer’s symptoms. According to experts, it is now necessary to understand the behavioral impact of removing these proteins from the brains of patients.

Side effects of treatment

The doctor Okamoto also points out that the drugs that combat the accumulation of proteins have serious side effects, such as cerebral edema, and need to be used in conjunction with imaging tests, such as magnetic resonance imaging.

“Almost 40% of patients can develop cerebral edema as side effects and, therefore, you have to be very careful when using this drug. You have to do a series of MRIs to prove the accumulation of proteins in the brain, and then you need periodic MRIs to monitor the side effects. It is an expensive and laborious process”, explains Okamoto.

The logic of the new drug currently being studied, lecanemab, is very similar to that of aducanumab. For experts, what companies need to explain is whether the 27% statistical improvement converts into real clinical benefits. So far, with the data released by the manufacturers, it is still not possible to say whether this percentage will translate into a significant improvement for the patient.

“The biological improvement is unequivocal with removal of amyloid plaques, but the clinical result has more modest results. What we have for lecanemab, so far, are just the results presented at the congress. Because of this, the reaction so far has been moderate optimism, because the approval process for aducanumab generated a lot of distrust, so we are cautious”, explains Cintra, from SBGG.

“But the controversy is now much less than in the case of aducanumab. Lecanemab did not have an approval process so full of doubts and reservations”, he adds. Cintra.

“Everyone is a bit scalded, but it is a door that opens, it is a hope”, he adds. Okamotodo Einstein.

What is Alzheimer’s disease

O Alzheimer It is a degenerative disease that causes brain tissue to deteriorate. This deterioration is caused by a series of mechanisms, among them, the accumulation of proteins. It causes a reduction in the number of active neurons and in the connections between the remaining neurons.

The deterioration that the disease causes in the brain also leads to a decline in cognitive functions, that is, the mental processes that allow us to carry out a series of tasks. The decline can manifest itself, for example, with episodes of memory loss and mental confusion, when the disease is in its mild stage.

It is these symptoms that usually trigger the alarm in family members, as happened with Jocelira’s daughters, who took their mother to the neurologist after an episode of recent memory loss.

“She went to the dentist but forgot where she had parked her car. This was an episode that marked us. That’s when I took my mother to the neurologist for the first time”, says Grolli.

As it progresses, Alzheimer’s also compromises the areas of the brain that control communication, reasoning and the senses, which can lead to the patient not being able to recognize some people, places or smells. Already in the most advanced stage, the disease leads to a total loss of communication capacity, and makes the patient dependent on caregivers.

The causes of Alzheimer’s are still not completely known. Scientists now believe that in people with early-onset Alzheimer’s, a genetic mutation may be responsible for the onset of brain deterioration.

For patients who begin experiencing symptoms after age 65, the causes likely include a combination of genetics and lifestyle factors, as well as natural changes in the brain that occur over time.

Even for those who already have the condition, combining a healthy diet with exercise and mentally stimulating activities can help slow the rate of cognitive decline.

It is no coincidence that neurologists and geriatricians recommend that family members encourage Alzheimer’s patients to maintain a healthy lifestyle.

Medicines and treatment

In addition to these precautions, there are still a series of drugs that are prescribed to treat patients with Alzheimer’s, and that can be obtained, with a prescription, from the Unified Health System (SUS).

The most commonly used are donepezil, rivastigmine, galantamine and memantine. All of these drugs work by regulating neurotransmitters, which are responsible for transmitting messages between neurons. Although they help to reduce symptoms and behavioral problems, these drugs do not change the disease process, that is, they do not stop or slow down the deterioration of the brain.

With a family history of Alzheimer’s, but still without any symptoms of the disease, Grolli has the profile that could benefit from the approval of new drugs, such as lecanemab, in the future. However, the psychologist’s wish, which went viral on TikTok when documenting the mother’s daily life with Alzheimer’s, was to be able to see the novelties in use in Jocelira’s treatment.

“It gives me a little hope, be it for me, for my children, for my sisters, if any of us develop Alzheimer’s. But it doesn’t take away my suffering because I really wanted to be able to use it today, on my mother, and I realize that everything is still a long way off”, concludes Grolli.

Technical review: Alexandre R. Marra, researcher at the Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEP) and permanent professor at the Graduate Program in Health Sciences at the Faculdade Israelita de Ciências da Saúde Albert Einstein (FICSAE).

Source: vidasaudavel.einstein.br

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